Can Essential Thrombocytosis (ET) lead to Myelofibrosis?

From the Guidelines

Yes, essential thrombocythemia (ET) can lead to myelofibrosis in some patients, with approximately 10-20% of patients with ET progressing to myelofibrosis over time, typically after many years of having ET. This progression is often referred to as post-ET myelofibrosis.

Key Points

• The transformation occurs due to the accumulation of genetic mutations in hematopoietic stem cells over time, as noted in the 2015 study by the International Working Group for Myeloproliferative Neoplasm Research and Treatment (IWG-MRT) 1.
• These mutations lead to increased production of inflammatory cytokines and growth factors, which stimulate the development of fibrosis in the bone marrow.
• Patients should be monitored regularly for signs of progression, including:
  • Worsening anemia
  • Increasing spleen size
  • Appearance of tear-drop shaped red blood cells on blood smears
  • Increasing bone marrow fibrosis on biopsy
• There is no specific treatment to prevent progression, but managing ET with appropriate therapies (such as hydroxyurea or interferon) may help slow the process, as recommended by the European LeukemiaNet (ELN) in 2011 1.
• If progression to myelofibrosis occurs, treatment approaches will need to be adjusted accordingly, with guidelines provided by the National Comprehensive Cancer Network (NCCN) in 2017 1.

Monitoring and Treatment

• Regular monitoring for signs of progression is crucial, with bone marrow aspirate and biopsy performed to rule out disease progression to myelofibrosis prior to the initiation of cytoreductive therapy, as suggested by the NCCN guidelines 1.
• The revised International Prognostic Score of Thrombosis for ET (IPSET-Thrombosis) is preferred for the risk stratification of ET, as noted in the 2016 study by Haider et al. 1.
• Aspirin should be used with caution in patients with acquired VWD, with higher-dose aspirin potentially appropriate in selected patients as clinically indicated, as recommended by the ELN in 2011 1.

From the Research

Essential Thrombocytosis (ET) and Myelofibrosis

• Essential Thrombocytosis (ET) is a myeloproliferative neoplasm that can transform into more aggressive myeloid neoplasms, including myelofibrosis 2, 3, 4
• The risk of transformation to myelofibrosis in ET patients is estimated to be around 9% at 15 years 3 and approximately 10% at a median of 8.5 years from diagnosis 4
• Driver mutations, such as JAK2, CALR, and MPL, are associated with distinct clinical features and may influence the risk of transformation to myelofibrosis 2, 3, 5
• The presence of certain mutations, such as MPL, has been associated with a higher risk of fibrotic progression 5

Risk Factors for Myelofibrosis in ET

• Advanced age is a risk factor for myelofibrosis in ET patients 6, 5
• The presence of certain mutations, such as JAK2 and MPL, may also increase the risk of myelofibrosis 5
• Other risk factors, such as leukocytosis and thrombosis, may also contribute to the development of myelofibrosis in ET patients 6, 5

Management of ET to Prevent Myelofibrosis

• The main goal of therapy in ET is to prevent thrombohemorrhagic complications and potentially reduce the risk of transformation to myelofibrosis 2, 3, 5, 4
• Low-dose aspirin and cytoreductive drugs, such as hydroxyurea, may be used to manage ET and reduce the risk of thrombosis and myelofibrosis 2, 3, 5, 4